RGFP136
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| Clinical data | |
|---|---|
| Other names | RGFP-136; Repligen-136; "Compound 136" |
| Drug class | Histone deacetylase inhibitor; HDAC3 inhibitor; Cognitive enhancer |
| ATC code |
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| Identifiers | |
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| PubChem CID | |
| ChemSpider | |
| ChEBI | |
| ChEMBL | |
| Chemical and physical data | |
| Formula | C20H24FN3O2 |
| Molar mass | 357.429 g·mol−1 |
| 3D model (JSmol) | |
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| Enzyme | IC50 (nM) |
|---|---|
| HDAC1 | 1,140–5,200 |
| HDAC2 | 3,000 |
| HDAC3 | 400–560 |
| HDAC4 | >180,000 |
| HDAC5 | >180,000 |
| HDAC6 | >180,000 |
| HDAC7 | >180,000 |
| HDAC8 | 13,200 |
| HDAC9 | ND |
| HDAC10 | ND |
| HDAC11 | ND |
| Refs: [1][2][3][4] | |
RGFP136, or RGFP-136, is a histone deacetylase (HDAC) inhibitor which is used in scientific research.[3][1][2][5] It is a modestly selective or preferential HDAC3 inhibitor, with an IC50 value of 400–560 nM, whereas the drug showed 2- to 13-fold lower inhibitory potency at HDAC1 and HDAC2 (IC50 = 1,140–5,200 nM and 3,000 nM, respectively).[1][2][3][4] It shows weak inhibition of HDAC8 and no inhibition of several other HDACs, including HDAC4, HDAC5, HDAC6, and HDAC7.[4] RGFP136 has been found to enhance long-term memory in rodents, which led to conclusions that HDAC3 is a critical regulator of long-term memory formation.[1][3] It has also been found to improve symptoms in an animal model of Friedreich ataxia.[5][2] The drug's pharmacokinetics have been studied and it is brain-penetrant in rodents.[1][3] RGFP136 was first described in the scientific literature by 2011.[1][5]
See also
[edit]References
[edit]- 1 2 3 4 5 6 McQuown SC, Barrett RM, Matheos DP, Post RJ, Rogge GA, Alenghat T, Mullican SE, Jones S, Rusche JR, Lazar MA, Wood MA (January 2011). "HDAC3 is a critical negative regulator of long-term memory formation". J Neurosci. 31 (2): 764–774. doi:10.1523/JNEUROSCI.5052-10.2011. PMC 3160172. PMID 21228185.
RGFP136, used in these studies, has an IC50 of 5.2 μM for HDAC1, 3.0 μM for HDAC2, and 0.4 μM for HDAC3 using purified recombinant HDACs. After systemic subcutaneous injection, the maximum drug concentration (Cmax) in the brain is 1.7 μM for a 30 mg/kg dose. This suggests that, after systemic administration, as in the data shown in Figure 6, RGFP136 is at a sufficient concentration in the brain to inhibit HDAC3 but perhaps not HDAC1 or HDAC2.
- 1 2 3 4 Rai M, Soragni E, Chou CJ, Barnes G, Jones S, Rusche JR, Gottesfeld JM, Pandolfo M (January 2010). "Two new pimelic diphenylamide HDAC inhibitors induce sustained frataxin upregulation in cells from Friedreich's ataxia patients and in a mouse model". PLOS ONE. 5 (1) e8825. Bibcode:2010PLoSO...5.8825R. doi:10.1371/journal.pone.0008825. PMC 2809102. PMID 20098685.
- 1 2 3 4 5 Nott, Alexi; Fass, Daniel M.; Haggarty, Stephen J.; Tsai, Li-Huei (2013). "HDAC Inhibitors as Novel Therapeutics in Aging and Alzheimer's Disease". Epigenetic Regulation in the Nervous System. Elsevier. pp. 225–248. doi:10.1016/b978-0-12-391494-1.00008-2. ISBN 978-0-12-391494-1. Retrieved 31 July 2026.
- 1 2 3 Abdallah DI, de Araujo ED, Patel NH, Hasan LS, Moriggl R, Krämer OH, Gunning PT (2023). "Medicinal chemistry advances in targeting class I histone deacetylases" (PDF). Explor Target Antitumor Ther. 4 (4): 757–779. doi:10.37349/etat.2023.00166. PMC 10497394. PMID 37711592.
- 1 2 3 Sandi C, Pinto RM, Al-Mahdawi S, Ezzatizadeh V, Barnes G, Jones S, Rusche JR, Gottesfeld JM, Pook MA (June 2011). "Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model". Neurobiol Dis. 42 (3): 496–505. doi:10.1016/j.nbd.2011.02.016. PMC 3107941. PMID 21397024.